Dr. Bailey-Wilson has been working for over 20 years to detect genetic risk factors for lung cancer and possible gene-gene and/or gene-environment interactions (5). The purpose of this study is to identify a gene or genes that contribute to lung cancer susceptibility. In this fiscal year, family data have been collected in Louisiana. Data collection is expected to continue for several more years. Dr. Bailey-Wilson is a founder of the Genetic Epidemiology of Lung Cancer Consortium (GELCC) for the purpose of obtaining additional family data from a large group of collaborative investigators. The first genome-wide significant linkage of a lung cancer susceptibility locus on chromosome 6q was published by us. A paper characterizing the effect of smoking in individuals predicted to be carriers of this 6q locus is submitted. In this fiscal year, we have continued sequencing candidate loci in this region and have published evidence that a risk allele at the gene RGS17 may have major effects on risk of lung cancer (6). This would represent the first major gene ever discovered for this cancer and is an exciting result. A new set of families has been genotyped for the same GWS markers and analyses are ongoing. Dr. Bailey-Wilson has applied our new propensity score method for including environmental risk factor data into non-parametric analyses (in LODPAL) to the new GWS data. A pilot genome-wide association study has confirmed evidence of association to SNPs in the nicotinic receptor subunit genes on 15q seen in 3 large population-based case-control studies (7,8). A SNP linkage panel was typed in all families and is being analyzed and a much larger GWAS on familial cases vs elderly, smoking controls will also be performed. Another major aim of Dr. Bailey-Wilson's research is to determine genetic risk factors in families with human prostate cancer. Papers published previously by our large group of collaborators have shown evidence of PRCA susceptibility genes in regions of chromosomes 1, 3p, 11q, 8 and X. These results have been followed up by intensive linkage analyses of additional families to markers in these regions and in other regions that showed some mild evidence of linkage in the initial genome scans. Previously, our group identified mutations in the ribonuclease-L (RNASEL) gene as being the locus in our chromosome 1 linkage region causing increased risk to prostate cancer and showed evidence that mutations in the MSR1 gene on chromosome 8 plays a role in prostate cancer risk. Dr. Bailey-Wilson's group is analyzing fine-mapping data in the African-American Hereditary Prostate Cancer (AAHPC) families. We work with the International Prostate Cancer Genetics Consortium (ICPCG) to try to localize prostate cancer loci more rapidly. A linkage meta-analysis is now underway to combine our African-American families from the AAHPC with those available from the ICPCG in order to increase power to detect loci that are of particular importance in this racial group. We are also collaborating with Dr. Johanna Schleutker in Finland and are currently analyzing a genome-wide linkage scan of a new set of 43 extended Finnish prostate cancer pedigrees. Another linkage metaanalysis of the Finnish families with the ICPCG families is also underway. We are also collaborating with Dr. Diptasri Mandal on linkage studies of prostate cancer in African-American men from Louisiana (4) As an adjunct to the family-based studies of prostate cancer described above, Dr. Bailey-Wilson is collaborating with Drs. Trent and Carpten of Tranlational Genomics, Drs. Cristina Leske and Barbara Nemesure of State University of New York at Stony Brook and Drs. Anselm Hennis and Lyndon Waterman of the University of the West Indies, in Barbados, on a study of the genetic epidemiology of prostate cancer and breast cancer in Barbados. These cancers occur at very high rates in the Barbadian population. Dr. Hennis'joint appointments in New York and Barbados have expedited this study. Data collection is underway for a large prostate case-control study, aiming for a sample of 1000 each. Several manuscripts on breast cancer risk factors in this population were published this year (1-3). We are analyzing fine-mapping SNPs on chromosome 8 to follow-up previous reports of linkage and association to prostate cancer in this region in other studies. We plan to carry out genome-wide association studies and other candidate gene studies in this population once sample accrual is completed.